Characterizing Neonatal Heart Maturation, Regeneration, and Scar Resolution Using Spatial Transcriptomics

Author:

Misra Adwiteeya,Baker Cameron D.,Pritchett Elizabeth M.ORCID,Burgos Villar Kimberly N.ORCID,Ashton John M.,Small Eric M.

Abstract

The neonatal mammalian heart exhibits a remarkable regenerative potential, which includes fibrotic scar resolution and the generation of new cardiomyocytes. To investigate the mechanisms facilitating heart repair after apical resection in neonatal mice, we conducted bulk and spatial transcriptomic analyses at regenerative and non-regenerative timepoints. Importantly, spatial transcriptomics provided near single-cell resolution, revealing distinct domains of atrial and ventricular myocardium that exhibit dynamic phenotypic alterations during postnatal heart maturation. Spatial transcriptomics also defined the cardiac scar, which transitions from a proliferative to secretory phenotype as the heart loses regenerative potential. The resolving scar is characterized by spatially and temporally restricted programs of inflammation, epicardium expansion and extracellular matrix production, metabolic reprogramming, lipogenic scar extrusion, and cardiomyocyte restoration. Finally, this study revealed the emergence of a regenerative border zone defined by immature cardiomyocyte markers and the robust expression of Sprr1a. Taken together, our study defines the spatially and temporally restricted gene programs that underlie neonatal heart regeneration and provides insight into cardio-restorative mechanisms supporting scar resolution.

Funder

National Heart Lung and Blood Institute

New York Department of Health - NYSTEM

American Heart Association

Publisher

MDPI AG

Subject

Pharmacology (medical),General Pharmacology, Toxicology and Pharmaceutics

Cited by 13 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Direct Cardiac Reprogramming in the Age of Computational Biology;Journal of Cardiovascular Development and Disease;2024-09-04

2. Multiplexed spatial transcriptomics methods and the application of expansion microscopy;Frontiers in Cell and Developmental Biology;2024-07-22

3. Identification and functional analysis of senescent cells in the cardiovascular system using omics approaches;American Journal of Physiology-Heart and Circulatory Physiology;2023-11-01

4. Cardiomyocyte-fibroblast crosstalk in the postnatal heart;Frontiers in Cell and Developmental Biology;2023-04-03

5. A guidebook of spatial transcriptomic technologies, data resources and analysis approaches;Computational and Structural Biotechnology Journal;2023

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3